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Growth impairment is a major public health issue for children in Tanzania. The question remains as to whether dietary mycotoxins play a role in compromising children's growth. We examined children's exposures to dietary aflatoxin and fumonisin and potential impacts on growth in 114 children under 36 months of age in Haydom, Tanzania. Plasma samples collected from the children at 24 months of age (N = 60) were analyzed for aflatoxin B1-lysine (AFB1-lys) adducts, and urine samples collected between 24 and 36 months of age (N = 94) were analyzed for urinary fumonisin B1 (UFB1). Anthropometric, socioeconomic, and nutritional parameters were measured and growth parameter z-scores were calculated for each child. Seventy-two percent of the children had detectable levels of AFB1-lys, with a mean level of 5.1 (95% CI: 3.5, 6.6) pg/mg albumin; and 80% had detectable levels of UFB1, with a mean of 1.3 (95% CI: 0.8, 1.8) ng/ml. This cohort had a 75% stunting rate [height-for-age z-scores (HAZ)

Abstract Background Neonatal mortality is a global challenge, with an estimated 1.3 million intrapartum stillbirths in 2015. The majority of these were found in low resource settings with limited options to intrapartum fetal heart monitoring devices. This trial compared frequency of abnormal fetal heart rate (FHR) detection and adverse perinatal outcomes (i.e. fresh stillbirths, 24-h neonatal deaths, admission to neonatal care unit) among women intermittently assessed by Doppler or fetoscope in a rural low-resource setting. Methods This was an open-label randomized controlled trial conducted at Haydom Lutheran Hospital from March 2013 through August 2015. Inclusion criteria were; women in labor, singleton, cephalic presentation, normal FHR on admission (120–160 beats/minute), and cervical dilatation ≤7 cm. Verbal consent was obtained. Results A total of 2684 women were recruited, 1309 in the Doppler and 1375 in the fetoscope arms, respectively. Abnormal FHR was detected in 55 (4.2%) vs 42 (3.1%). (RR = 1.38; 95%CI: 0.93, 2.04) in the Doppler and fetoscope arms, respectively. Bag mask ventilation was performed in 80 (6.1%) vs 82 (6.0%). (RR = 1.03; 95%CI: 0.76, 1.38) of neonates, and adverse perinatal outcome was comparable 32(2.4%) vs 35(2.5%). (RR = 0.9; 95%CI: 0.59, 1.54), in the Doppler and fetoscope arms, respectively. Conclusion This trial failed to demonstrate a statistically significant difference in the detection of abnormal FHR between intermittently used Doppler and fetoscope and adverse perinatal outcomes. However, FHR measurements were not performed as often as recommended by international guidelines. Conducting a randomized controlled study in rural settings with limited resources is associated with major challenges. Trial registration This clinical trial was registered on April 2013 with registration number NCT01869582.

Background: Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. Methods: Non-diarrheal stool samples (N = 22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N = 6363) and plasma alpha-1-acid glycoprotein (AGP) (N = 2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0–2 years of age. Findings: Children in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated. Interpretation: The large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation. Funding: Bill & Melinda Gates Foundation.

BackgroundShigella infections cause inflammation, which has been hypothesized to mediate the associations between Shigella and child development outcomes among children in low-resource settings. We aimed to assess whether early life inflammation and Shigella infections affect school-aged growth and cognitive outcomes from 6-8 years of age.Methodology/principal findingsWe conducted follow-up assessments of anthropometry, reasoning skills, and verbal fluency in 451 children at 6-8 years of age in the Brazil, Tanzania, and South Africa sites of MAL-ED, a longitudinal birth cohort study. We estimated the associations between Shigella burden and inflammation with linear growth at 2, 5, and 6-8 years of age, and with the cognitive test scores using linear regression and adjusting for potential confounding variables. We also assessed whether inflammation mediated the associations between Shigella and school-aged outcomes using a regression-based approach to mediation analysis. A high prevalence of Shigella was associated with a 0.32 (95% CI: 0.08, 0.56) z-score lower height-for-age z-score (HAZ) at 6-8 years compared to a low prevalence of Shigella. Intestinal inflammation had a smaller association with HAZ at 6-8 years. Shigella burden had small and consistently negative associations with cognitive outcomes in Brazil and Tanzania, but not South Africa, and the estimates were not statistically significant. Systemic inflammation was strongly associated with lower verbal fluency scores in Brazil (semantic fluency z-score difference: -0.57, 95% CI: -1.05, -0.10; phonemic fluency z-score difference: -0.48, 95% CI: -0.93, -0.03). There was no evidence that intestinal inflammation mediated the association between Shigella and HAZ or cognitive outcomes.Conclusions/significanceWhile Shigella infections were consistently associated with long-term deficits in linear growth, the estimates of the negative associations between Shigella and cognitive outcomes were imprecise and only observed in the Brazil and Tanzania sites. Systemic inflammation was strongly associated with lower semantic and phonemic fluency scores in Brazil only, highlighting the site-specificity of effects.

Background While head circumference (HC) has been related to intracranial volume and brain size, its association with cognitive function remains unclear. We sought to understand the relationship among various biological and socioeconomic risk factors, HC and cognitive development.Methods We analysed data across resource-poor settings in Bangladesh, India, Nepal, Peru, South Africa and Tanzania from the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development longitudinal birth cohort study. Participating children were enrolled and followed up between 2009 and 2014. A final sample of 1210 children aged 0–24 months were included in the analyses. The main outcomes were HC for age Z-score and cognitive, gross motor and language scores from Bayley Scales of Infant Development-III tests. Length, weight and HC were measured monthly, and cognitive tests were administered at 6, 15 and 24 months of age. To disentangle the associations between risk factors and HC from linear growth and to distinguish the direct and indirect effects of these risk factors on cognitive function, we conducted mediation analysis using longitudinal models to account for all data measured during follow-up.Results Average HC-for-age Z-score (HCAZ) was −0.54 (95% CI −0.47 to −0.62) near birth and −1.01 (95% CI −0.94 to −1.08) at 24 months. Children with higher enrolment weight (p

Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (